Fetal malnutrition due to impaired nutrient transport has been proposed as a mechanism for the teratogenicity of ethanol (EtOH). The nutrition of chronic alcoholics is frequently suboptimal which, if associated with placental dysfunction, may increase the potential for fetal malnutrition. The similarity between EtOH-associated fetal abnormalities and the neuropathology of gestational zinc (Zn) deficiency has been recognized previously. Because of the prevalence of Zn deficiency in chronic alcoholics, it is reasonable to test the hypothesis that maternal EtOH ingestion, coupled with restricted Zn intake, may critically depress placental Zn transport, induce fetal Zn deficiency, and impair brain development. The proposed studies will explore these concepts by measuring 65Zn transport, placental blood flow, maternal and fetal tissue Zn levels, and the microchemical architecture of adult cortex after exposure to EtOH and Zn deficiency in utero. Pregnant rats will be exposed to either short-term Zn restriction and EtOH during 2 gestational ages [days 10-12 (neuroblast proliferation) or days 18-20 (neuronal migration)] OR fed liquid diets of varying Zn/EtOH composition throughout gestation. Ad libitum or pair-fed Zn-supplemented controls will receive isocaloric carbohydrate substitution for EtOH. Zn metabolism will be assessed by: a) placental 65Zn transport and uptake by fetal brain and other tissues and b) Zn pool size. Maternal and fetal Zn status will be related to placental blood flow in the same animal using the 57Co-labeled microspheres. Pregnancy outcome will be determined by examining the fetal weight, resorptions, and gross malformation. If EtOH/Zn deficiency interferes with neuronal proliferation or migration, then specific biochemical changes may be detected in adult cortex. I propose to analyze such rats for DNA, ganglioside (a synaptic marker), distribution of ganglioside species, and galactocerebroside (a myelin marker) in cortical laminae employing microchemical techniques used previously by myself and correlate these measurements with Zn status and placental blood flow. Demonstrating that EtOH and Zn restriction interact to produce biochemical changes in brain by inhibiting placental Zn transport would support the hypothesis that EtOH-associated fetal abnormalities result from fetal malnutrition. Such observations would provide a greater impetus for dietary supplementation of chronic alcoholic mothers to ameliorate the potential toxic effects of EtOH during gestation.